Lower CXCR3 expression in both patients with neovascular AMD and advanced stages of chronic myeloproliferative blood cancers

PLoS One. 2022 Jun 16;17(6):e0269960. doi: 10.1371/journal.pone.0269960. eCollection 2022.


Purpose: Peripheral T cell CXCR3 expression has been found uniquely lower in patients having neovascular age-related macular degeneration (nAMD) than in healthy individuals. The CXCR3-axis has been shown to have angiostatic and antifibrotic properties. We have recently investigated systemic markers in patients with myeloproliferative neoplasms (MPNs) because of their higher prevalence of AMD, and we have observed higher systemic chronic low-grade inflammation and immunosenescence signs in MPNs with drusen (MPNd) compared to those with normal retinas (MPNn). The MPNs evolve in a biological continuum from early cancer-stages (essential thrombocytosis, polycythemia vera) to the advanced myelofibrosis stage. Especially myelofibrosis is characterized by bone marrow angiogenesis and fibrosis, similarly to retinal observations in nAMD. We speculate if we can find lower CXCR3 expression in MPNs, particularly myelofibrosis and if differences are seen between MPNd and MPNn. We also wanted to compare expression in nAMD and intermediate (i)AMD.

Methods: Patients in this cross-sectional study were 29 nAMD, 28 iAMD, 35 MPNd, and 27 MPNn. We performed flowcytometry on blood to measure CXCR3 expression.

Results: CD8+CXCR3 expression in nAMD was 6,1%, significantly lower than in iAMD 16%, MPNd 11%, MPNn 12% (p-values<0.05). Similar results were seen for CD4+CXCR3 expression. We also found CXCR3 expression decreasing over the MPN-continuum. For instance, in myelofibrosis, intermediate monocytes expression was 6.2%, significantly lower than 18% in ET and 18% in PV (p-values<0.05).

Conclusions: We find CXCR3 downregulation on T-cells and some monocyte subset in nAMD compared to iAMD, MPNd, and MPNn, in line with previous nAMD studies. We also find CXCR3 downregulation in most monocyte subsets over the MPN continuum. Systemic leukocyte CXCR3 expression could both be involved in changes seen in the retina and the bone marrow. Further understanding the CXCR3-axis in AMD and MPNs may elucidate underlying pathogenic mechanisms and reveal new targets for treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors
  • Chronic Disease
  • Cross-Sectional Studies
  • Humans
  • Leukemia* / complications
  • Myeloproliferative Disorders* / complications
  • Myeloproliferative Disorders* / diagnosis
  • Myeloproliferative Disorders* / genetics
  • Polycythemia Vera* / diagnosis
  • Primary Myelofibrosis*
  • Receptors, CXCR3 / genetics
  • Thrombocythemia, Essential*
  • Vascular Endothelial Growth Factor A
  • Visual Acuity
  • Wet Macular Degeneration* / complications


  • Angiogenesis Inhibitors
  • CXCR3 protein, human
  • Receptors, CXCR3
  • Vascular Endothelial Growth Factor A

Grants and funding

The first author CL is a Ph.D. candidate at the University of Copenhagen (UCPH). The Ph.D. project was funded by “Fight for Sight, Denmark” and Region Zealand’s Research Promotion Fund, Denmark. This work submitted is a partial requirement for a Ph.D. at UCPH. The sponsors are public and non-profit organizations. They had no role in the study's design and conduct; collection, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publicationHCH reports grants from Novartis outside the submitted work and is on the Advisory Board of AOP Orphan. The rest of the authors have no financial disclosures.